Shimizu A, Ishii E, Kuwahara N, Arai T, Kanzaki G, Higo S, Kajimoto Y, Nagasaka S, Masuda Y, Fukuda Y
Department of Pathology, Nippon Medical School, Tokyo, Japan.
Transplant Proc. 2013 Jun;45(5):1743-7. doi: 10.1016/j.transproceed.2013.02.045.
The category of chronic antibody-mediated rejection (AMR) is not included in Banff schema for liver allograft rejection. In the present study, we examined the pathology of chronic rejection using rat liver transplantation. Orthotopic liver transplantation from Lewis to BN rats was performed without immunosuppression, and with or without HA reconstruction. We studied grafts at day 120 for arterialized and day 39 for nonarterialized transplants focusing on the immunoglobulin G (IgG) deposition and the pathologic characteristics of rejection. About 20% of arterialized grafts survived more than 120 days. Between day 7 and day 120, T-cell infiltration to arterialized grafts was accompanied by IgG deposition in portal veins, hepatic arteries, and bile ducts in portal areas, sinusoids and hepatocytes. At day 120, arterialized grafts were morphologically characterized by late chronic rejection with IgG deposition, intraluminal portal veins fibrosis, intimal fibrous thickening of hepatic arteries, diffuse sinusoidal fibrosis, as well as injury and loss of bile ducts due to fibrosis. The severities of T cell-mediated rejection and AMR were higher in nonarterialized than arterialized grafts. Nonarterialized Lewis liver grafts in BN rats were rejected by day 39, as characterized by late chronic rejection with IgG deposition and cellular infiltration. In conclusion, chronic AMR may be involved in chronic rejection of liver transplantations. When chronic AMR was involved in chronic liver graft rejection, typical late morphological changes emerged within a short period.
慢性抗体介导性排斥反应(AMR)类别未包含在肝移植排斥反应的Banff分类法中。在本研究中,我们利用大鼠肝移植来研究慢性排斥反应的病理学。在未进行免疫抑制以及进行或未进行HA重建的情况下,进行了从Lewis大鼠到BN大鼠的原位肝移植。我们重点研究了免疫球蛋白G(IgG)沉积和排斥反应的病理特征,对动脉化移植在第120天以及非动脉化移植在第39天的移植物进行了研究。约20%的动脉化移植物存活超过120天。在第7天至第120天之间,动脉化移植物中的T细胞浸润伴随着IgG在门静脉、肝动脉以及门管区的胆管、肝血窦和肝细胞中的沉积。在第120天,动脉化移植物的形态学特征为伴有IgG沉积的晚期慢性排斥反应、门静脉腔内纤维化、肝动脉内膜纤维增厚、弥漫性肝血窦纤维化以及因纤维化导致的胆管损伤和丧失。非动脉化移植物中T细胞介导的排斥反应和AMR的严重程度高于动脉化移植物。BN大鼠中的非动脉化Lewis肝移植物在第39天被排斥,其特征为伴有IgG沉积和细胞浸润的晚期慢性排斥反应。总之,慢性AMR可能参与肝移植的慢性排斥反应。当慢性AMR参与慢性肝移植物排斥反应时,典型的晚期形态学改变会在短时间内出现。